Telaprevir/boceprevir is a protease inhibitor that can be used as antiviral drug. By way of example, telaprevir inhibits the hepatitis C virus NS3-4A serine protease.
Although some processes for the synthesis of telaprevir/boceprevir and its pharmaceutically acceptable salts are available, it is an object of the present invention to provide alternative processes, in particular enhanced processes that overcome at least one of the problems of the prior art processes.
WO 2007/138928 A1 discloses the preparation of a compound having the following formula:
(R11=H) by using optically active oxazolines as intermediates.
WO 2007/109023 A1 describes the preparation of the same compound via epoxidation of an α,β-unsaturated carboxyamide, azidation of the epoxide, reduction of the azide group to provide an amine and subsequent racemic resolution.
WO 2009/114633 A1 also describes a synthesis for the above compound starting from norvaline. In order to elongate the chain of norvaline, a cyanide addition is performed.
WO2009/152474 A2 describes a process for the preparation of 3-amino-N-cyclopropyl-2-hydroxyalkane amide derivatives as key intermediates in the production of HCV inhibitors. The synthesis route comprises a step of reacting an aminoaldehyde with a cyclopropyl isocyanide to obtain an 3-amino-2-hydroxycarboxylic acid amide.
Yamamoto (Journal of the American Chemical Society 1993, 115, 1151 and Tetrahedron 1994, 50, 9, 2785) describes a process for the synthesis of building blocks for the synthesis of taxol. The synthesis includes the use of an imine, a silyl enol ether, a Lewis acid (LA) and chiral boron reagents (see FIG. 1).